This study examines the clinical features as well as molecular and biochemical correlates of heritable disorders of connective tissue; Marfan Syndrome, Ehlers-Danlos Syndrome (EDS) and Stickler Syndrome, as well as related disorders such as Familial Aneurysm Syndromes and Fibromuscular Dysplasia. To date, approximately 650 subjects have been enrolled in the study. Autonomic dysfunction with increased sympathetic tone and post orthostatic tachycardia has been documented in 30% of the subjects with EDS, based on frequency domain analysis of the Holter monitor data and blood pressure measurements. Bone densitometry studies have shown that premature osteoporosis and osteopenia are very common in the EDS and Marfan patients, and may be correlated with specific mutations. MRI studies of the cervical and lumbar spine are also carried out on subjects. We have recently found that approximately one third of patients have Chiari I malformations and 85% of the subjects have significant abnormalities pertaining to the spine including hernitated discs, spondylolisthesis, and dural ectasia. We have noted previously unrecognized complications of EDS, including the development of rheumatoid arthritis in older persons with EDS (in 15% of our cohort), increased incidence of clinically significant sleep disorders, and a high prevalence of unfavorable lipid profiles as compared to NHANES averages in all age groups. Endocrine abnormalities in HDCT have been analyzed. Approximately 30% of the males with Vascular EDS and Marfan syndrome have hypogonadism and accompanying low bone density. We have identified a Familial Aneurysm family where the phenotype segregates with a premature stop codon in COL5A1. A previously unrecognized hereditary disorder of connective tissue, fibromuscular dysplasia (FMD) with connective tissue features has been identified within subjects enrolled in the study. [unreadable] [unreadable] In the connective tissue cohort, complications such as disc disease in the spine, vascular fragility, gonadal failure, done density loss, chronic pain and musculoskeletal impairment appear at a much younger age. The information obtained from this study will not only help the treatment of effected patients, but will also provide insights into the pathological processes of normal aging.